Demineralized bone implants

ABSTRACT

Selectively demineralized bone-derived implants are provided. In one embodiment, a bone sheet for implantation includes a demineralized field surrounding mineralized regions. In another embodiment, a bone defect filler includes a demineralized cancellous bone section in a first geometry. The first geometry is compressible and dryable to a second geometry smaller than the first geometry, and the second geometry is expandable and rehydratable to a third geometry larger than the second geometry.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of prior patent applicationSer. No. 09/927,335, filed Aug. 13, 2001, which in turn claims thebenefit of Provisional Application No. 60/271,745 filed Feb. 28, 2001under 35 U.S.C. § 119(e). The entire contents of these applications areexpressly incorporated herein by reference thereto.

FIELD OF THE INVENTION

[0002] The invention is related to implants formed from bone. Moreparticularly, the invention is related to implants formed from partiallydemineralized or demineralized bone.

BACKGROUND OF THE INVENTION

[0003] Bone grafts have become an important and accepted means fortreating bone fractures and defects. In the United States alone,approximately half a million bone grafting procedures are performedannually, directed to a diverse array of medical interventions forcomplications such as fractures involving bone loss, injuries or otherconditions necessitating immobilization by fusion (such as for the spineor joints), and other bone defects that may be present due to trauma,infection, or disease. Bone grafting involves the surgicaltransplantation of pieces of bone within the body, and generally iseffectuated through the use of graft material acquired from a humansource. This is primarily due to the limited applicability ofxenografts, transplants from another species.

[0004] Orthopedic autografts or autogenous grafts involve source boneacquired from the same individual that will receive the transplantation.Thus, this type of transplant moves bony material from one location in abody to another location in the same body, and has the advantage ofproducing minimal immunological complications. It is not always possibleor even desirable to use an autograft. The acquisition of bone materialfrom the body of a patient typically requires a separate operation fromthe implantation procedure. Furthermore, the removal of material,oftentimes involving the use of healthy material from the pelvic area orribs, has the tendency to result in additional patient discomfort duringrehabilitation, particularly at the location of the material removal.Grafts formed from synthetic material have also been developed, but thedifficulty in mimicking the properties of bone limits the efficacy ofthese implants.

[0005] As a result of the challenges posed by autografts and syntheticgrafts, many orthopedic procedures alternatively involve the use ofallografts, which are bone grafts from other human sources (normallycadavers). The bone grafts, for example, are placed in a host bone andserve as the substructure for supporting new bone tissue growth from thehost bone. The grafts are sculpted to assume a shape that is appropriatefor insertion at the fracture or defect area, and often require fixationto that area as by screws or pins. Due to the availability of allograftsource material, and the widespread acceptance of this material in themedical community, the use of allograft tissues is certain to expand inthe field of musculoskeletal surgery.

[0006] With respect to the overall structure of a given bone, themechanical properties vary throughout the bone. For example, a long bone(leg bone) such as the femur has both compact bone and spongy bone.Cortical bone, the compact and dense bone that surrounds the marrowcavity, is generally solid and thus carries the majority of the load inmajor bones. Cancellous bone, the spongy inner bone, is generally porousand ductile, and when compared to cortical bone is only about one-thirdto one-quarter as dense, one-tenth to one-twentieth as stiff, but fivetimes as ductile. While cancellous bone has a tensile strength of about10-20 MPa and a density of about 0.7, cortical bone has a tensilestrength of about 100-200 MPa and a density of about 2. Additionally,the strain to failure of cancellous bone is about 5-7%, while corticalbone can only withstand 1-3% strain before failure. It should also benoted that these mechanical characteristics may degrade as a result ofnumerous factors such as any chemical treatment applied to the bonematerial, and the manner of storage after removal but prior toimplantation (i.e. drying of the bone). In addition, bones have a graindirection similar to the grain found in wood, and thus the strength ofthe bone varies depending on the orientation of the grain.

[0007] Notably, implants of cancellous bone incorporate more readilywith the surrounding host bone, due to the superior osteoconductivenature of cancellous bone as compared to cortical bone. Furthermore,cancellous bone from different regions of the body is known to have arange of porosities. For example, cancellous bone in the iliac crest hasa different porosity from cancellous bone in a femoral head. Thus, thedesign of an implant using cancellous bone may be tailored tospecifically incorporate material of a desired porosity.

[0008] Demineralization of cortical, cancellous, and corticocancellousbone of autograft, allograft, and xenograft types is known. In one form,bone powder or chips are chemically processed using an acid such ashydrochloric acid, chelating agents, electrolysis or other treatments.The demineralization treatment removes the minerals contained in thenatural bone, leaving collagen fibers with bone growth factors includingbone morphogenic protein (BMP).

[0009] The use of expandable materials as a prosthetic element isdisclosed in U.S. Pat. No. 5,545,222 to Bonutti. Materials disclosedwhich expand when they come in contact with water or other fluidsinclude PEEK (polyether-etherketone), a desiccated biodegradablematerial, or a desiccated allograft. As an example, a tendon can becompressed in a desiccated state, and as it imbibes water it expands andcreates a firmer lock or tighter fit in the host site.

[0010] A shaped, swollen demineralized bone and its use in bone repairis disclosed in U.S. Pat. No. 5,298,254 to Prewett et al. In general,cortical allogeneic bone tissue is preferred as the source of bone.Demineralized bone is contacted with a biocompatible swelling agent fora period of time sufficient to cause swelling of the piece.

[0011] A flexible implant using partially demineralized bone isdisclosed in U.S. Pat. No. 6,206,923 to Boyd et al. The bone implant hasa first substantially rigid portion and a second substantially rigidportion which are joined by an intermediate portion that has been atleast partially demineralized to create an area of flexibility in thebone implant. The pair of rigid bone portions cooperate to providesupport for spacing between adjacent vertebra.

[0012] Demineralized bone has been disclosed for use as artificialligaments in U.S. Pat. No. 5,092,887 to Gendler. Completely or partiallydemineralized cortical bone is sliced in strips and rods ofapproximately 0.1-1.5 centimeters wide and 0.1-1.5 centimeters thickwith compliant elasticity and longitudinal strength similar to naturalligaments and tendons. The strips or rods are used as artificialligaments for in vivo replacement, repair and augmentation of damagedligaments, tendons or other fibrous tissue that permanently connectsfirst and second body members such as the femur and tibia. Disclosure ofa segmentally demineralized bone implant is found in U.S. Pat. No.6,090,998 to Grooms et al. The implant comprises a first mineralizedportion or segment, and a second, flexible, demineralized portion orsegment that are produced by machining a piece of cortical bone.

[0013] A textured, demineralized, and unitary mammalian bone section forproviding a rigid, foraminous, collagen scaffold for allogenic skeletalreconstruction is disclosed in U.S. Pat. No. 5,112,354 to Sires.Texturing or pore formation is carried out prior to demineralization topermit completeness of demineralization and additionally promoteosteoinduction due to the increased surface area. Pores of between 200μm and 2000 μm are created with a laser. The depth of the holes in thebone may be varied.

[0014] Also disclosed in U.S. Pat. No. 5,899,939 to Boyce et al. is abone-derived implant for load-supporting applications. The implant isformed of one or more layers of fully mineralized or partiallydemineralized cortical bone and, optionally, one or more layers of someother material such as fully demineralized bone or mineral substancessuch as hydroxyapatite. The layers constituting the implant areassembled into a unitary structure to provide an implant withload-supporting properties. Superimposed layers are assembled into aunitary structure such as with biologically compatible adhesives.

[0015] U.S. Pat. No. 5,556,430 discloses flexible membranes producedfrom organic bone matrix for skeletal repair and reconstruction.Completely or partially demineralized organic bone is sliced into thinsheets. The bone may be perforated prior to demineralization, toincrease the osteoinductivity of the final bone product. Similarly, U.S.Pat. No. 5,298,254 to Prewett et al. discloses demineralized bone slicedinto a thin sheet which can be used to patch an injury.

[0016] A cortical bone interference screw is disclosed in U.S. Pat. No.6,045,554 to Grooms et al. The interference screw has a cortical surfaceinto which a self-tapping thread is machined.

[0017] In addition, U.S. Pat. No. 5,053,049 to Campbell discloses theuse of milling, grinding, and pulverizing to produce pulverized bonewith the desired particle size. The pulverized bone can then be combinedwith any suitable biologically compatible or inert carrier substance,which should have a consistency that imparts the desired flexibletexture to the pulverized bone/carrier suspension, or should solidify tothe desired consistency after molding or casting.

[0018] Despite these developments, there exists a need for implantsformed from partially or fully demineralized cancellous bone.Furthermore, there exists a need for implants formed of bone that havebeen selectively masked during demineralization so that portions of thebone are at least partially demineralized while other portions aresubstantially remain in the mineralized state.

SUMMARY OF THE INVENTION

[0019] The present invention relates to a method of providing a boneimplant including: demineralizing a cancellous bone section having afirst geometry; compressing the bone section from the first geometry toa second geometry smaller than the first geometry; drying the bonesection while the bone section has approximately the second geometry;and inserting the bone section into a space. When the bone section isinserted into the space, the bone section may be at least partiallysurrounded by a wall while having approximately the second geometry. Themethod may further include expanding the bone section from the secondgeometry to a third geometry larger than the second geometry, as well asallowing the bone section to expand to contact the wall. The bonesection may be expanded by rehydrating.

[0020] The invention also relates to a method of maintaining a distancebetween vertebral bodies including: demineralizing a bone section havinga first geometry; drying the bone section; inserting the bone section inbetween vertebral bodies; and expanding the bone section to a secondgeometry. The bone section may be demineralized cortical bone. Thedrying step may include freeze drying the bone section, and the bonesection may be expanded by hydrating. The method further may includecompressing the bone section. The bone section may be cancellous bone.The method may be used to replace the nucleus of a vertebral disc.

[0021] The invention further relates to a method of replacing nucleus ofa vertebral disc including: providing a demineralized cortical bonesection having a first geometry; inserting the bone section in betweenvertebral bodies; and expanding the bone section to a second geometry.The bone section may be expanded by hydrating, and may be expanded to aheight in the second geometry which is larger than the height in thefirst geometry. The bone section in the second geometry may have a topsurface and a bottom surface, each of the top and bottom surfaces beingconfigured to approximately match a concave vertebral endplate. The topand bottom surfaces may be convex with a radius of between about 50 mmand about 70 mm.

[0022] In addition, the invention relates to an implant includingdemineralized cancellous bone capable of being softened and compressedinto a smaller first shape and hardened in said first shape, and capableof expanding into a second shape larger than said first shape whenresoftened and permitted to expand. The bone may be softened byhydration and may be hardened by dehydration. The bone may be configuredand dimensioned to by received in an anatomical void. The first shapemay be smaller than the anatomical void, and the second shape may beabout the same as the shape of the anatomical void. The second shapealso may span a lateral dimension of the anatomical void. The implantmay further include cortical bone.

[0023] In some embodiments, the implant is configured and dimensioned tobe disposed in a burr hole or void in the cranial region of the skull.The implant may form a burr hole cap including an upper cortical bonesection and a lower, demineralized cancellous bone section, at least thelower section being sized to fill the burr hole when in the expandedsecond shape. In some embodiments, the implant is generally T-shaped andincludes an upper cortical bone section and a lower, demineralizedcancellous bone section. In the expanded second shape, at least thelower section may be sized to contact walls of the void. The uppersection may have an arcuate portion for generally matching the contourof the skull. Slits may be included extending through at least a portionof one or both of the cortical bone and cancellous bone.

[0024] The present invention further is related to a bone sheet forimplantation, the sheet including a demineralized field surroundingmineralized regions.

[0025] The present invention also is related to a bone defect fillerincluding a demineralized cancellous bone section in a first geometry.The first geometry is compressible and dryable to a second geometrysmaller than the first geometry, and the second geometry is expandableand rehydratable to a third geometry larger than the second geometry.

[0026] The present invention is further related to a method of fillingan open region with cancellous bone, the method including:demineralizing a section of cancellous bone; compressing the section;drying the compressed section; inserting the section into the openregion; rehydrating the section; and allowing the section to expand tofill the open region.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Preferred features of the present invention are disclosed in theaccompanying drawings, wherein:

[0028]FIG. 1 shows a bone section of a femur;

[0029] FIGS. 2-3 show a cortical shell of the present invention;

[0030]FIG. 4 shows a cortical sheet formed from the cortical shell ofFIG. 2;

[0031]FIG. 4A shows a spiral cortical sheet formed from the corticalshell of FIG. 2;

[0032]FIG. 4B shows a cortical sheet according to an alternativeembodiment;

[0033] FIGS. 5-7 show various forms of cancellous bone of the presentinvention;

[0034]FIG. 8 shows a cage for filling with cancellous bone of FIG. 7;

[0035]FIG. 8A shows a cage filled with cancellous bone of FIG. 7;

[0036]FIG. 9 shows a femur section for filling with demineralizedcancellous bone of FIG. 6;

[0037]FIG. 9A shows a femur section filled with demineralized cancellousbone of FIG. 6;

[0038]FIG. 10 shows a partially demineralized cancellous bone cylinderof the present invention;

[0039]FIG. 11 shows a woven bone implant of the present invention;

[0040]FIG. 12 shows a demineralized cortical bone implant for nucleusreplacement according to the present invention;

[0041] FIGS. 13-15 show ligament replacements using bone implants of thepresent invention;

[0042] FIGS. 16-18 show the use of partially demineralized bone strutsfor disc replacement according to the present invention;

[0043] FIGS. 19-21 show a bendable implant of the present invention;

[0044] FIGS. 22-23 show bone cords of the present invention;

[0045]FIG. 24 shows a cortico-cancellous demineralized bone of thepresent invention;

[0046] FIGS. 25-27 show cranial flap void and burr hole fillingaccording to the present invention;

[0047] FIGS. 28-29 show dogbone-shaped plates of the present invention;

[0048]FIG. 30 shows a cortical tack or suture anchor of the presentinvention; and

[0049]FIG. 31 shows an embodiment of a ribbed bone sheet.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0050] The present invention in one embodiment is directed to animplantable bone sheet that exhibits semi-pliable properties overportions of the sheet, while exhibiting semi-rigid properties over otherportions. The variation in properties is achieved by the selectivedemineralization of bone preferably selected from a femur, tibia,humerus, fibula, ulna, and radius. The terms “demineralization,”“demineralized” and “at least partially demineralized” as used hereinare intended to refer to fully demineralized bone or partiallydemineralized bone. The term “fully demineralized” refers to bone wherethe minerals have been substantially completely removed from the bonewhereas the term “partially demineralized” refers to bone where at leastsome portion of the minerals have been removed. As will become apparent,the degree of demineralization will depend upon the characteristicssought to be achieved in the implant.

[0051] Turning to FIG. 1, a bone section 10 of a femur has an innersurface 12, and an outer surface 14 which initially conforms to thenatural shape of the bone. The wall thickness of bone section 10 varies,as indicated by thicknesses T₁, T₂, and T₃. As shown in FIG. 2, bonesection 10 may be machined to have a relatively uniform wall thicknessT₄, forming a cortical shell 16. Initially, cortical shell 16 isgenerally rigid, and holes 18 are formed from machined inner surface 20to machined outer surface 22. Holes 18 may be provided in repeatingpatterns, or as desired.

[0052] In order to selectively screen areas of cortical shell 16 fromdirect contact with treatments such as hydrochloric acid, chelatingagents, electrolysis, or other suitable treatments, a pair of maskingelements 24 are disposed proximate each hole 18, with one maskingelement 24 disposed on machined inner surface 20 and the other disposedon machined outer surface 22. When tightly retained against surfaces 20,22, masking elements 24 seal portions of cortical shell 16 fromsurrounding treatment fluids and reactions. In one preferred embodiment,masking elements 24 are toroidal in shape and have some flexibility suchthat the toroidal shape may be compressed to bear against the surface ofcortical shell 16. Suitable masking elements include rubbery washers,o-rings, and grommets, which preferably have resistance to chemicalattack from the treatments to which cortical shell 16 will be subjected.In order to create a secure seal, masking elements 24 are retained inplace, using screws 26, the heads 28 of which bear against one maskingelement 24 and the threaded shafts 30 of which extend through thealigned pair of masking elements 24 and hole 18. Preferably, the screwsare formed of a material that does not react with or otherwisecontaminate cortical shell 16, such as a suitable polymer. Pressure isapplied to masking elements 24 by threadably receiving a nut 32 on eachthreaded shaft 30 to bear against the other of the masking elements 24in each pair that is not in contact with a head 28 of screw 26. Apartial side view of a pair of masking elements 24 retained againstcortical shell 16 are shown in FIG. 3. Although heads 28 of screws 26are shown disposed inside cortical shell 16 adjacent machined innersurface 20 and nuts 32 are shown disposed outside cortical shell 16adjacent machined outer surface 22, the reverse configuration is alsocontemplated.

[0053] Other masking elements 24 are also suitable for the presentinvention. For example, press-fit elastic rings with outercircumferential grooves may be used to seal the regions of corticalshell 16 around each hole 18, as long as adequate surface contact and/orpressure can be applied by the rings to prevent leakage of treatmentliquids therebetween. Alternatively, tapes or paints may be applied toserve as masking elements 24 to seal particular regions. For example, anair dry synthetic rubber coating may be used by dipping or otherwisepainting select regions of an implant to mask the regions fromtreatment. Preferably, the aforementioned masking techniques are notonly resistant to the bone treatments, but are readily removed followingtreatment.

[0054] Various configurations of masking elements 24 can be chosen toprovide the desired amount of protection from treatments. As will now beexplained, the present configuration is useful for providing limitedregions of mineralized bone surrounded by a field of demineralized bone.Such a configuration is particularly useful, for example, in permittingthe production of a generally flexible sheet of demineralized corticalbone with mineralized, rigid regions bordering holes for use inreceiving fasteners. Thus, surgical procedures necessitating theattachment of demineralized cortical bone for eventual assimilation intoneighboring tissue may make use of a flexible sheet of the presentinvention that includes regions, for example, for receiving bone screws,with the regions being resistant to tearing or other damage duringinstallation and stressing of the bone sheet.

[0055] After suitable masking procedures have been completed, corticalshell 16 is immersed or otherwise treated with a demineralizing agent.While the untreated cortical shell 16 initially possessed rigidproperties, the selectively demineralized cortical shell 16 exhibitsrubbery, elastic-like properties. Turning to FIG. 4, the treatedcortical shell 16 has been cut across its length, such that a sheet 34is formed. Sheet 34 includes a demineralized field 36 surroundingmineralized regions 38 which are disposed about holes 18. Although notshown, a near mirror image is present on both surfaces 20, 22, andgenerally extends across the thickness of sheet 34.

[0056] Because the selectively demineralized cortical sheet ismalleable, and thus generally can be made to conform to the shape of agiven anatomical region, such a cortical sheet may also find use inorthopaedic procedures as a “wrapping” material to surround areasrequiring surgical intervention, or as a sealing material over defectareas such as regions excised due to tumors. In one embodiment, thecortical sheet may be used as a bridging agent for a bad fracture, andin another embodiment it may be used to encapsulate bone inside abarrier to retain blood and other products in a localized area.Furthermore, the sheet may serve as a patch, such as to cover regions ofthe skull temporarily removed to permit surgical access to the cranialarea. Also, if the sheet is perforated sufficiently, it may serve as amesh. Preferably, the perforations are substantially smaller thanfastener holes provided in the sheet. In addition, the demineralizedcortical sheet may be used to surround an iliac crest harvest, insteadof the polymer sheet otherwise used. Preferably, the cortical sheet hasa thickness of between about 0.5 mm and about 3 mm.

[0057] Notably, the above selective demineralization process may be usedwith bone portions already in sheet-like form prior to selectivedemineralization treatment. For example, strips of cortical bone may beprecut from bone section 10, with holes 18 drilled accordingly. In thecase of a cortical shell 16 as discussed above, however, the shell-likestructure is preferably kept intact until after treatment due to itsrigid and thus fracture-prone characteristics. Although the applicationof masking elements 24 is more complicated with a shell geometry thanwith a sheet or strip geometry, the production of selectivelydemineralized sheets of significantly greater area is possible with theshell-like structures.

[0058] In an alternate embodiment shown in FIG. 4A, a bone section 10′may be cut in spiral form 37 so that the overall outer and innergeometry of the bone need not be extensively machined to achieve auniform wall thickness. Longitudinal cuts 39 also may be made such thatindividual sheets may be produced from the spiral. The cuts can beformed at regular distances through the spiral form 37 so that sheets ofdesired sizes can be produced. Thus, demineralized or partiallydemineralized sheets may be formed using this technique.

[0059] The mineralized regions 38 which are formed in the demineralizedfield 36 of sheet 34 may have a configuration other than shown in FIG.4. For example, mineralized regions 38 may be larger or smaller thanshown and may have a different configuration as shown in FIG. 4B. Inaddition, mineralized regions 38 may be connected together for exampleby a connecting strip or strut 38′ of mineralized bone. The struts 38′may be configured to be directed substantially along parallel axis toprovide the sheet with different characteristics in differentdirections. In this manner, the connecting struts may provide the sheetwith a preferred orientation. Struts 38″ also may be provided and may beoriented in an orthagonal or other direction from strut 38′ to providethe desired properties for sheet 34 in the direction of strut 38″. Bychanging the shape and size of mineralized regions 38 and struts 38′ and38″, a sheet having desired directional properties may be designed.

[0060] The present invention is also directed to selectivelydemineralized cancellous bone for filling voids, bone defects, or otherregions such as the cavities inside spinal cages. While mineralizedcancellous bone may function in some load bearing capacity in wet anddry conditions, demineralized cancellous bone acts like a sponge when itis wet and exhibits “memory” properties when dried and subsequentlyrehydrated. For example, turning to FIGS. 5-9, a block 40 of cancellousbone may initially be provided in a demineralized state, with an initialgeometry and volume V₁. Block 40 may be submersed in water, andpermitted to assume a soft, hydrated state in which it may be compressedto a smaller configuration such as pellet 42 with new volume V₂<V₁. Thecompressed pellet 42 is then allowed to dry, and it hardens in thepellet-like configuration instead of the block-like configuration. Itshould also be noted the when demineralized bone dries, it furthershrinks, but it will re-expand when rehydrated. To regain the block-likeconfiguration of block 40, pellet 42 is subsequently rehydrated andpermitted to expand back to its original shape and regain soft, spongyproperties. Because of this “memory” effect, the demineralized,cancellous bone may be supplied in standard geometries that can be usedto fill correspondingly sized cavities, or in geometries that are usedto expand and fill any given shape smaller than or equal to theirexpanded size. In addition, the degree of expansion from compression(i.e., as a function of the volume of void to be filled) may be used toproduce a demineralized cancellous body with particular porosity.Swelling agents other than or in addition to water may also be employed.

[0061] In one embodiment, a bone section such as femur section 50 shownin FIG. 9 with an internal channel 52 may be loaded with a pellet 42,and when the pellet 42 is permitted to rehydrate, pellet 42 expands tofill the channel 52 as shown in FIG. 9A. This is particularly useful forirregularly shaped volumes as shown with channel 52.

[0062] In another embodiment, block 40 may also be compressed to acylindrical configuration such as a cylinder 44. Cylinder 44 isparticularly well adapted for use with a hollow cage 46 with internalcavity 47 and perforations 48, shown in FIG. 8. When a suitably sizedcylinder 44 is placed within cage 46 and rehydrated, cylinder 44 expandsto fill internal cavity 47 and perforations 48 as shown in FIG. 8A. Thecage 46 may or may not be provided with perforations 48 but expansion ofthe pellet 42 or cylinder 44 or other dried cancellous bone section inperforations 48 helps to retain the bone section within the cage orshell.

[0063] In yet another embodiment, a pellet 42 or cylinder 44 may bedelivered to a defect region in the body, and rehydrated to fill thedefect. Other geometries and degrees of compression are contemplated aswell, including a flat, pancake-like configuration, a donut-likeconfiguration, and a dumbell configuration which may be used to expandwithin a defect such as a through-hole and plug either end of thethrough-hole. Based on the degree of compression, as well as the degreeof demineralization, control of the degree of porosity of thedemineralized cancellous bone insert may be achieved.

[0064] With reference to FIG. 10, a partially demineralized cancellousbone cylinder 60 is shown. Cylinder 60 includes mineralized, rigidportions 62, 64 and a demineralized, sponge-like section 66therebetween. As discussed above with respect to selectively screeningareas of a bone portion from direct contact with chemical treatments,portions 62, 64 are preferably masked during treatment of cylinder 60.In addition, while section 66 is exposed to demineralization treatment,the degree of demineralization can be controlled as a function of theduration of treatment (i.e., submersion time in demineralizing agent)and the strength of the treatment medium (i.e., dilute or strong acid).Thus, the degree of “sponginess” or resiliency may be selected to meet aparticular clinical application. Fully or partially demineralizedcylinders such as cylinder 60 may be used, for example, to fill bonydefects caused by the removal of bone screws during subsequent surgicalprocedures, to fill bony defects resulting from the removal of diseasedbone, or as burr hole covers necessitated by cranial surgery.

[0065] Turning again to demineralized cortical bone, the ligament-like,pliable properties of the bone resulting from the demineralizationtreatment advantageously may be used. Because the properties of bonevary as a function of direction with respect to the bone grains, sheetsof pliable bone may be woven together from strips of bone cut atparticular orientations with respect to the grains. Woven bone implant70 is shown in FIG. 11. Strips 72 running generally parallel to eachother along a first direction form columns which are woven together withstrips 74 that are running generally parallel to each other along asecond grain direction forming rows. By disposing the strips in thismanner, the properties of woven bone implant advantageously may betailored to a particular need, for example through the selectiveorientation of the grains of criss-crossing bone strips. In someembodiments, strips 72, 74 of woven bone implant 70 may each bemineralized, demineralized, or partially demineralized. Also, each strip72, 74 may include mineralized regions and demineralized regions. Theorientation of the grain direction of each of the strips may further beused to tailor the properties of the woven bone implant 70.

[0066] As an illustrative, non-limiting example, bone strips 72, 74 mayhave an overall length less than or equal to the maximum length of abone from which the strips are produced. Thus, bone strips 72, 74, forexample, may be 12 inches in length if a bone has such an overalllength. Moreover, the bone strips 72 may be much shorter than an overallbone length, and thus, for example one-inch bone strips 72 may be used.Bone strips 72, 74 may have a width of between about 1 mm and about 6mm, and a thickness of between about 0.5 mm and about 2 mm. In anotherembodiment, bone strips 72, 74 may have a width of about 5 mm and athickness of about 1 mm. The bone strips 72, 74 may be woven in asimilar fashion to a basket, as shown for example in FIG. 11. Theresulting sheets may have the same uses and applications, for example,as the sheet described in FIG. 4.

[0067] In another exemplary embodiment, bone strips preferably at leastabout 1 mm in thickness and width may be braided, similar to carbonfiber, in uni-directional, bi-directional, two-dimensional, andthree-dimensional braid configurations. In yet another exemplaryembodiment, individual bone fiber strands, preferably with a thicknessof less than about 0.5 mm, may be braided and/or woven to create a bonecloth. An increase in strength may be realized by alternating graindirections, thereby also permitting larger overall implants to beproduced. Braids additionally may incorporate other materials, such aslaminations, bonding agents, and/or bone inducing substances.

[0068] Demineralized bone may also be used in nucleus replacement. Thenucleus pulposus is the inner gel-like portion of an intervertebral discconsisting of proteoglycans and a collagen meshwork. Younger individualspossess water in this region, but older individuals lose water resultingin disc degeneration and deydration. Such difficulties are commonlyknown as disc herniation—the nucleus pulposus herniates through theannulus when this occurs. In one preferred embodiment, as shown in FIG.12, a demineralized cortical bone implant 80 having an initial height H₁is freeze-dried so that it shrinks to a second height H₂, with H₁>H₂. Inthe smaller configuration, implant 80 is loosely inserted into adegenerated disc region to provide support, and subsequently rehydratedso that it expands to provide rubber-like structural support so thatproper disc height is regained. An implant 80 used in nucleoplastypreferably has an initial height H₁ at its largest dimension betweenabout 3 mm and about 17 mm. Top and bottom surfaces 81 a, 81 bpreferably may be radiused to approximate the concavity of the vertebralendplates, and preferably have a radius of between about 50 mm and about70 mm. In one exemplary embodiment, top and bottom surfaces 81 a, 81 bare protruding and convex with a radius of about 60 mm.

[0069] Referring to FIGS. 13-15, the use of demineralized and partiallydemineralized cortical bone in ligament replacements is shown. Ademineralized cortical bone, generally rectangular plate 82 may befastened in place using fasteners 84 located in corners of the plate. Inother embodiments, alternate shapes of plate 82 may be used. The platemay be used, for example, to replace the anterior longitudinal ligament(ALL) that extends over the length of the lumbar spine anterior to thevertebral bodies, or the interspinous ligament (ISL) that attachesadjoining spinous processes and serves, for example, to limit forwardbending. As shown for example in FIG. 14, partially demineralizedcortical bone for use in ALL may include a demineralized section 86bordered above and below by mineralized sections 88. The mineralizedsections retain rigidity, and thus are most suitable for containingfastener holes 90. Referring to FIG. 15, a lateral view of the spine isshown with a partially demineralized cortical bone 92 used to replace anISL disposed adjacent the spinous process.

[0070] Turning to FIGS. 16-18, the use of demineralized or partiallydemineralized femoral struts for disc replacement is shown. Thepertinent spinal structures are shown in FIG. 16, with a pair ofvertebral bodies 100 disposed adjacent a disc 102. A generallycylindrical femoral strut 104 with teeth 106 and a central hole 108,includes a demineralized central portion 110 and mineralized portions112. Once femoral strut 104 is implanted between vertebral bodies 100,mineralized portions 112 advantageously fuse with vertebral bodies 100,while demineralized central portion 110 mimics the behavior of disc-likecollagen.

[0071] Another demineralized cortical bone implant 120 is shown in FIGS.19-21. Implant 120 preferably includes a partially demineralized layer122 and a mineralized, mechanically stronger layer 124. Slits 126 arecut in mineralized layer 124, and the pliability of layer 122 permitsimplant 120 to be bent as shown in FIGS. 20-21.

[0072] Referring to FIGS. 22-23, demineralized cortical bone may also beused in laminoplasty, the replacement of bone at the site of a previousexcision in order to reestablish structural support and protection ofthe spinal cord. In laminectomy, the lamina and spinous process havebeen removed, while in laminotomy only a portion of the lamina isremoved. A demineralized cortical bone cord 130 with mineralizedcortical portions 132 and demineralized portions 134 to provideflexibility. Cord 130 may have free ends suitable for fixation, forexample, to the exposed portions of the lamina following removal of alamina section. Alternatively, a demineralized cortical bone cord 140with mineralized cortical portions 142 and demineralized central portion144 may similarly be used. Cords 130, 140 are used to bridge the gapcreated by the tissue excision. As discussed above with respect to otherembodiments of the present invention, fastener holes may be located inthe mineralized portions of the cortical bone cords.

[0073] Turning to FIG. 24, a section 150 of cortico-cancellousdemineralized bone taken, for example, from the wall where thetransition from the midshaft to the condyle of a bone occurs. A layer ofcancellous bone 152 and a layer of cortical bone 154 may be jointlydemineralized, resulting in a bone implant with two types of properties.Such selectively demineralized bone is particularly useful inmaxillofacial procedures including reconstructive procedures as well aselective procedures such as face lifts, chin augmentations, cheekenhancements, and eye brow lifts. The demineralized region is relativelysoft, while the mineralized region remains relatively hard and thusbetter accommodates implant fixation screws.

[0074] As shown in FIGS. 25-27, demineralized bone also can be used as acranial flap void filler. In particular, during craniotomies, which aresurgical procedures performed in the treatment of various brain problemssuch as tumors, aneurysms, blood clots, head injuries, abscesses, andthe like, access to the brain is achieved by the creation of a hole inthe bone that defines the skull. The hole or “window” in the skull isusually created by identifying the area of the brain to which access isneeded, drilling several holes into the skull near the periphery of thisarea, inserting a cutting tool into one of the holes, and making cutsfrom one hole to another. Removal of the cut-out area of the skull,generally referred to as a bone flap, allows the desired access to thebrain. After the desired medical or surgical procedure on the brain hasbeen performed, the bone flap must be replaced and held in a stableposition to allow the skull to heal.

[0075] Typically, when the bone flap is replaced in the region fromwhich it was removed, gaps or voids remain between the bone flap andskull due to the cutting operation. To fill the gaps or voids, pliable,demineralized cortical bone may be used. For example, pliable,demineralized cortical bone may be inserted in the void 168 formed inthe cranial region 166 of the skull. In one preferred embodiment, agenerally T-shaped bone implant 160 is inserted in void 168 so thatfirst portion 162 fits in void 168, while second portion 164 abuts thetop of cranial region 166 of the skull. Preferably, first portion 162 ofbone implant 160 is demineralized to provide flexibility, while secondportion 164 remains mineralized bone to provide stiffness. To provideflexibility, slits 165 a may extend through parts of second portion 164.Similarly, slits 165 b may extend through a part of first portion 162,and may be aligned with slits 165 a. In one exemplary embodiment,implant 160 is provided with an upper side 169 a of second portion 164that may be arcuate in cross-section and preferably concave. In anotherexemplary embodiment, second portion 164 is provided with lower arcuateportions 169 b that generally match the contour of the skull in theregion of use. An arcuate, upper portion 169 c also may be provided.Such a flexible implant 160 thus permits the filling of a curved channelsuch as a void 168. In an alternate embodiment, demineralized cancellousbone may be used.

[0076] Burr holes 170 may be filled with covers formed of fully orpartially demineralized bone as well. A burr hole cap 172 is shown inFIG. 27, with an upper portion 174 and a lower portion 176. Burr holecap 172 may be formed of cortico-cancellous bone, with a cortical upperportion 174 and a lower cancellous portion 176. In addition, a portionof cap 172 may be demineralized, such as upper portion 174, whileanother portion such as lower portion 176 may be mineralized.

[0077] The “memory” properties of demineralized cancellous bone, asdiscussed above, may also be used to provide selectively compressibleportions of a bone implant such as T-shaped bone implant 160 or burrhole cap 172. For example, in one preferred embodiment, lower portion176 of cap 172 is demineralized cancellous bone, while upper portion 174is mineralized or demineralized cortical bone. The demineralizedcancellous bone of lower portion 176 may be hydrated so that it assumesa soft state in which it may be compressed to a smaller configuration,and then subsequently allowed to dry and harden in the compressed state.After insertion of the compressed lower portion 176 into a burr hole170, lower portion 176 may be rehydrated and permitted to expand back toits original shape, regaining soft, spongy properties, and filling burrhole 170.

[0078] In an alternate embodiment of T-shaped bone implant 160, firstportion 162 is formed of demineralized cancellous bone and fits in void168, while second portion 164 is formed of cortical bone and is disposedproximate the top of cranial region 166 of the skull. Thus, theaforementioned “memory” properties of demineralized cancellous bone maybe used to provide a desired fit of T-shaped bone implant 160 in void168.

[0079] In yet another alternate embodiment, T-shaped bone implant 160and one or more burr hole caps 172 may be provided as a unitarystructure. The variable dimensions of the void 168 and burr holes 170may be accommodated by the expandable “memory” properties of thedemineralized cancellous bone portion.

[0080] Turning to FIGS. 28-29, additional embodiments of implantsproduced from partially demineralized cortical bone are shown.Preferably, dogbone-shaped or dumbbell-shaped plates 180, 186 are formedof a unitary body with a pair of generally symmetrical side portionshaving a first width W₁, and a central portion disposed therebetweenhaving a second width W₂ which is less than the first width. Plate 180includes mineralized portions 182 and demineralized portion 184. Portion184 is disposed diagonally across plate 180 to facilitate movement. Inthe embodiment of plate 186, demineralized portions 188, 190, which maybe perpendicular or otherwise transversely disposed with respect to eachother, permit angulation of plate 186 with more than one degree offreedom. Such dogbone plates may be used, for example, in thin areas ofthe face where fixation is required. In one embodiment, plates 180, 186may have, for example, an overall length of between about 10 mm andabout 20 mm, as measured for example along the central longitudinal axisdefined by demineralized portion 188 of plate 186. In addition, plates180, 186 preferably may have, for example, a maximum width W₁ betweenabout 4 mm and about 7 mm, as measured for example along the axisdefined by demineralized portion 190 of plate 186, and may have, forexample, a thickness between about 1 mm and about 3 mm. In one exemplaryembodiment, a dogbone-shaped plate 180, 186 has a length of about 15 mm,a maximum width of about 5 mm, and a thickness of about 2 mm.

[0081] Referring to FIG. 30, a cortical tack or suture anchor 210 isshown, including a head 212, eyelet 214, and shaft 215 with ribs 216.All areas of suture anchor 210 except ribs 216 may be masked andthereafter subjected to a demineralizing agent. Following treatment,head 212 remains hard, while demineralized ribs 216 are malleable. Onceinserted into a hole in bone, the demineralized ribs 216 of sutureanchor 210 permit an interference fit, and may serve as resiliento-rings. Thus, when a suture anchor 210 is pressed into a hole, thedemineralized o-ring structure provides holding power to resist removalor backout of the suture anchor from the hole.

[0082] In FIG. 31 an implantable bone sheet 134 that exhibits selectivedirectional properties is disclosed. Bone sheet 134 may be formed ofmineralized or demineralized bone, and may be produced from, and in amanner similar to, cylindrical tube or shell 16 of FIGS. 1 and 2. Sheet134 has a longitudinal axis 150 and a cross axis 155 perpendicular tolongitudinal axis 150. A plurality of corrugations or ribs 165 extendalong the length L of the sheet 134 parallel to longitudinal axis 150.The ribs 150 provide a greater thickness and stiffness to the sheet. Inparticular the ribs resist bending in the direction along which theyextend while providing greater flexibility in the opposite direction.The sheet is more flexible in the direction opposite the direction ofthe ribs and may be formed into a tube similar to that shown in FIGS. 2and 8 (but with the ribs, although the perforations may or may not beincluded).

[0083] The ribs may be of any shape, for example, square or trianglecross-section. As shown in FIG. 31, the ribs may be formed havingpointed or rounded peaks 166 and may form troughs 168 therebetween. Thetroughs 168 may have a flat section 169 which separates adjacent ribs165. Instead of ribs 134, projections such as, for example, teeth may beused. By varying the thickness, height, shape, number and direction ofthe ribs 165 or projections, the sheet 134 can be tailor designed tohave the desired properties in the desired directions.

[0084] The sheet 134 may be formed to have a mineralized bone section170 and demineralized section 175. The demineralized section providesflexibility to the sheet while the mineralized section providesstiffness. Alternatively, the sheet 134 may be formed by machining abone section, whether it be in the form of a sheet or precursor tube, tohave the ribs or other projections and then subjecting the sheet or tubeto demineralization agents. The sheet or tube may be subjected todemineralization from one or both sides. Where the sheet or tube issubject to demineralization agents from side 185, the sheet may take theform shown in FIG. 31 where it has a demineralized section 175 and amineralized section 170. The demineralizing agents also may attack onlythe side 180, having the ribs as shown in FIG. 31, in which case becauseof the greater thickness at the ribs, the demineralized section of thesheet will take a shape that conforms more closely to the outerconfiguration of the ribbed side of the sheet. In other words, theinterface between the demineralized section and the mineralized sectionmay not have the straight planar configuration as shown in FIG. 31 butinstead will approximate the shape of the ribs.

[0085] If the demineralizing agent were applied to both sides of thesheet or tube, the resulting sheet may have an interior mineralizedsection which corresponds roughly to the ribs because of the greaterthickness of the sheet where the ribs are located. Depending upon thetime with which the demineralizing agent is applied to the bone section,the thickness of the mineralized section can be varied. If themineralized agents were applied to both sides for a sufficient amount,the resulting sheet or tube may have a plurality of interior discretemineralized sections between and dispersed in the field of demineralizedbone. As a result of the ribs or projections which provide a greaterlocalized thickness, a mineralized section may remain while itssurrounding areas where the sheet may be less thick has no mineralizedbone remaining. The ribs or projections are configured to provide thedesired flexibility in the desired direction while retaining the desiredstiffness in the desired direction. The sheet 134 is preferably formedof cortical bone and the grain of bone material may extend in the sameor a different direction than the ribs 165.

[0086] The side 185 may be substantially smooth, or may have ribs asillustrated for side 180 in FIG. 31, or other projections. Side 185 mayhave a ribbed design similar to or different than side 180. For example,the ribs on side 185 may extend in the same direction as side 180 or mayextend in a direction transverse or orthagonal to the ribs of side 180.It will be appreciated that while FIG. 31 has been illustrated withribs, the sheet may alternatively have projections such as teeth on oneor both sides. The sheet also may be provided with perforations or besubject to masking selective areas as illustrated in FIGS. 1-4.

[0087] As discussed herein, demineralized cortical, cancellous, andcorticocancellous bone may be used as a relatively soft substance forenhancing anatomical areas such as during plastic surgery, or forfilling defect regions resulting from disease, congenital conditions, orsurgical procedures. Demineralized bone of the present invention mayalso be formed into screws, which advantageously are less brittle thanscrews formed of mineralized bone. In particular, selectivedemineralization may be undertaken for portions of a screw structure sothat a surgeon applying the screw receives tactile feedback from thepliable, demineralized portion when certain stress is reached.Angulation control also is possible by selectively demineralizing thescrew.

[0088] Other processes of the present invention include the recovery ofthe minerals removed from the demineralizing of the bones, and thereintroduction of these minerals into bone implants. In addition, thevarious machining operations for the production of bone implants producedifferent bone fibers, bone powder and particulates, bone chips, orcombinations thereof. Milling of cortical bone can produce long andshort fibers. The thickness and length of the fibers is a function ofthe blade design, milling speed of the milling operation, and the feedrate of the bone. Grinding can produce powder or particulates of varyingsizes, which may be sieved to separate the powder or particulates intodesired size ranges. Moreover, bone chips may be produced by a latheoperation. The properties and usage of these by-products vary dependingupon the degree of any demineralization. For example, cortical longfibers produced by milling of bone may be treated in hydrochloric acidfor an extended period of time, and allowed to demineralize to a mushyconsistency. The demineralized long fibers tend to clump together.Additional pressing means may be used to further encourage clumping.Demineralized cortical fibers may be pressed together in a wet orsemi-wet state in a compression molding operation to produce a part of adesired geometry. Once dry, the solid part has significant strength.

[0089] While various descriptions of the present invention are describedabove, it should be understood that the various features can be usedsingly or in any combination thereof. Therefore, this invention is notto be limited to only the specifically preferred embodiments depictedherein.

[0090] Further, it should be understood that variations andmodifications within the spirit and scope of the invention may occur tothose skilled in the art to which the invention pertains. For example, ademineralized cortical shell may be sized to behave like a rubber band,and used for a similar purpose. Accordingly, all expedient modificationsreadily attainable by one versed in the art from the disclosure setforth herein that are within the scope and spirit of the presentinvention are to be included as further embodiments of the presentinvention. The scope of the present invention is accordingly defined asset forth in the appended claims.

What is claimed is:
 1. A method of providing a bone implant comprising:demineralizing a block of cancellous bone having a first geometry;wetting the block; compressing the block from the first geometry to asecond geometry smaller than the first geometry; permitting the block toharden after the block has been compressed to the second geometry. 2.The method of claim 1, wherein the second geometry is configured anddimensioned as a pellet.
 3. The method of claim 1, wherein the secondgeometry is configured and dimensioned as a cylinder.
 4. The method ofclaim 1, wherein the second geometry is configured and dimensioned as agenerally flat shape.
 5. The method of claim 1, wherein the secondgeometry is configured and dimensioned as a donut-like shape.
 6. Themethod of claim 1, wherein the second geometry is configured anddimensioned as a dumbell shape.
 7. The method of claim 1, furthercomprising: exposing the block to a swelling agent.
 8. The method ofclaim 1, further comprising: inserting the block into an anatomicalspace.
 9. The method of claim 8, further comprising: re-expanding theblock to a third geometry larger than the second geometry.
 10. Themethod of claim 9, wherein the third geometry is smaller than the firstgeometry.
 11. The method of claim 1, further comprising: inserting theblock into a spinal cage.
 12. The method of claim 11, furthercomprising: re-expanding the block to a third geometry larger than thesecond geometry.
 13. The method of claim 12, wherein the third geometryis smaller than the first geometry.
 14. The method of claim 1, furthercomprising: wherein the step of wetting the block comprises hydratingthe block.
 15. A method of providing a bone implant comprising:demineralizing a block of cancellous bone having a first configuration;softening the block; compressing the block from the first configurationto a second configuration smaller than the first configuration;permitting the block to harden after the block has been compressed tothe second configuration.
 16. The method of claim 15, wherein the stepof softening the block comprises applying at least one of water and aswelling agent to the block.
 17. The method of claim 15, furthercomprising: inserting the block into a space; re-expanding the block toa third configuration larger than the second configuration.
 18. A methodof providing a bone implant comprising: softening a block ofdemineralized, cancellous bone having a first volume; compressing theblock to a second volume smaller than the first volume; permitting theblock to harden after the block has been compressed to the secondvolume.
 19. The method of claim 18, further comprising: inserting theblock into a space; re-expanding the block to a third volume larger thanthe second volume.
 20. The method of claim 18, wherein the space is ananatomical space.